Cereus grandiflorus flower extract modulates genes involved in circadian rhythm and cell migration to favorize night cell processes
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Presented by: Gabrielle Misset
Introduction
Cereus grandiflorus belonging to the Cactaceae familly (cactus), is native from the desert regions of the West Indies, tropical America, and Mexico. Its flowers, sweet scented, bloom with white petals at night for six hours only. This medicinal flower is traditionally used to treat heart diseases. It is rich in sugars such as glucose, fructose, amino acids, acids (citric, fumaric, malonic…), alkaloids (including cactine) and flavonoids.
It has been demonstrated that many metabolic pathways are under the control of clock genes[1], present in each cell of the body that function in a circadian and autonomous manner. It is well demonstrated that the release of melatonin during nighttime plays a role in the circadian rhythm and involves interaction with clock genes.[2]
At skin level, these clock genes control the rate and intensity of expression of genes involved in the quality of the skin barrier, in hydration[3], in defense and / or regeneration of the skin.Interestingly, during nighttime the circadian rhythm favorize the regeneration processes.[4]
Objective: To assess if C. grandiflorus extract might improve keratinocytes migration and modulate the circadian rhythm, as compared to melatonin.
Methods: An artificial human keratinocyte wound healing test was performed, keratinocytes were inoculated in culture medium in a 96-well plate dedicated to the analysis of migration (ref. Platypus OrisTMCollagen I Coated Plate).
A few hours after seeding the cells and after adhesion of the cells, the medium was replaced with test medium and the cells were treated with the C. grandiflorus extract during 24H. to observe its action on cells migration to recover an empty zone. After 24H pre-incubation, the covers were removed and image analyzes were performed at times 14, 18 and 24 hours.
A second test carried out on human keratinocytes studied the modulation of the C. grandiflorus extract on 14 circadian genes expression on basal situation during 48h via a qPCR array with a positive control, melatonin at 67 µg/ml and 200 µg/ml. The evaluation has been performed at different timeline: 1, 3, 6, 24, 36 and 48 hours to follow modulation due to circadian rhythm.
Results: In the artificial keratinocyte wound healing test, C. grandiflorus extract (0.3mg/mL) significantly stimulated cells migration (on average 128% of the control (no treatment) over the 3 analysis times). A qPCR array on circadian genes demonstrated that both, melatonin and C. grandiflorus extract modulate 6 circadian genes, whom PER1, CRY1 and the melatonin receptors, in the same way.
Conclusion: The C. grandiflorus extract stimulates keratinocyte migration and modulates specific genes involved in circadian rhythm, these two actions are major processes that participate to skin night regeneration.
[1] Dyar KA, Eckel-Mahan KL. Circadian Metabolomics in Time and Space. Front Neurosci. 2017;11:369. Published 2017 Jul 11.
[2] Pevet P, Challet E. Melatonin: both master clock output and internal time-giver in the circadian clocks network. J Physiol Paris. 2011 Dec;105(4-6):170-82
[3] Matsunaga N, Itcho K, Hamamura K, Ikeda E, Ikeyama H, Furuichi Y, Watanabe M, Koyanagi S, Ohdo S. 24-hour rhythm of aquaporin-3 function in the epidermis is regulated by molecular clocks. J Invest Dermatol. 2014 Jun;134(6):1636-1644.
[4] Janich P, Toufighi K, Solanas G, Luis NM, Minkwitz S, Serrano L, Lehner B, Benitah SA. Human epidermal stem cell function is regulated by circadian oscillations. Cell Stem Cell. 2013 Dec 5;13(6):745-53.
Cereus grandiflorus belonging to the Cactaceae familly (cactus), is native from the desert regions of the West Indies, tropical America, and Mexico. Its flowers, sweet scented, bloom with white petals at night for six hours only. This medicinal flower is traditionally used to treat heart diseases. It is rich in sugars such as glucose, fructose, amino acids, acids (citric, fumaric, malonic…), alkaloids (including cactine) and flavonoids.
It has been demonstrated that many metabolic pathways are under the control of clock genes[1], present in each cell of the body that function in a circadian and autonomous manner. It is well demonstrated that the release of melatonin during nighttime plays a role in the circadian rhythm and involves interaction with clock genes.[2]
At skin level, these clock genes control the rate and intensity of expression of genes involved in the quality of the skin barrier, in hydration[3], in defense and / or regeneration of the skin.Interestingly, during nighttime the circadian rhythm favorize the regeneration processes.[4]
Objective: To assess if C. grandiflorus extract might improve keratinocytes migration and modulate the circadian rhythm, as compared to melatonin.
Methods: An artificial human keratinocyte wound healing test was performed, keratinocytes were inoculated in culture medium in a 96-well plate dedicated to the analysis of migration (ref. Platypus OrisTMCollagen I Coated Plate).
A few hours after seeding the cells and after adhesion of the cells, the medium was replaced with test medium and the cells were treated with the C. grandiflorus extract during 24H. to observe its action on cells migration to recover an empty zone. After 24H pre-incubation, the covers were removed and image analyzes were performed at times 14, 18 and 24 hours.
A second test carried out on human keratinocytes studied the modulation of the C. grandiflorus extract on 14 circadian genes expression on basal situation during 48h via a qPCR array with a positive control, melatonin at 67 µg/ml and 200 µg/ml. The evaluation has been performed at different timeline: 1, 3, 6, 24, 36 and 48 hours to follow modulation due to circadian rhythm.
Results: In the artificial keratinocyte wound healing test, C. grandiflorus extract (0.3mg/mL) significantly stimulated cells migration (on average 128% of the control (no treatment) over the 3 analysis times). A qPCR array on circadian genes demonstrated that both, melatonin and C. grandiflorus extract modulate 6 circadian genes, whom PER1, CRY1 and the melatonin receptors, in the same way.
Conclusion: The C. grandiflorus extract stimulates keratinocyte migration and modulates specific genes involved in circadian rhythm, these two actions are major processes that participate to skin night regeneration.
[1] Dyar KA, Eckel-Mahan KL. Circadian Metabolomics in Time and Space. Front Neurosci. 2017;11:369. Published 2017 Jul 11.
[2] Pevet P, Challet E. Melatonin: both master clock output and internal time-giver in the circadian clocks network. J Physiol Paris. 2011 Dec;105(4-6):170-82
[3] Matsunaga N, Itcho K, Hamamura K, Ikeda E, Ikeyama H, Furuichi Y, Watanabe M, Koyanagi S, Ohdo S. 24-hour rhythm of aquaporin-3 function in the epidermis is regulated by molecular clocks. J Invest Dermatol. 2014 Jun;134(6):1636-1644.
[4] Janich P, Toufighi K, Solanas G, Luis NM, Minkwitz S, Serrano L, Lehner B, Benitah SA. Human epidermal stem cell function is regulated by circadian oscillations. Cell Stem Cell. 2013 Dec 5;13(6):745-53.